The overall goal of this application is to examine the effects of cannabis use on decision-making processes in adolescents using magnetic resonance imaging techniques and neurocognitive measures of reward discounting, loss discounting, and ambiguity preference. Adolescence is a critical developmental period during which sub-optimal decision-making may increase vulnerability to substance abuse. Two critical aspects of adolescent decision-making related to substance abuse may be the interplay between immediate and delayed rewards and losses as well as choices between certain and ambiguous (unknown) options. Investigation of the neural correlates of decision-making in cannabis abusing adolescents is particularly important because cannabis abuse may compromise still developing neural circuits important for decision-making and lead to subsequent poor choices. It has been suggested that adolescent risk taking may be a result of hypersensitive reward systems that contribute to novelty seeking. Given that adolescence is a period of high novelty seeking, a preference for ambiguity or the unknown may be associated with drug use. Underdeveloped cortical structures, such as prefrontal cortex, may also lead to myopia for future outcomes. Substance abuse has been associated with increased devaluation of delayed rewards and it has been shown that adolescents discount delayed rewards more than adults. Research on discounting of losses has been limited thus far. However, shortsightedness during adolescence may lead to increased preference for larger delayed losses over immediate small losses. We propose that the study of altered choice preference and the patterns of neural activity under different decision-making conditions will reveal important distinctions between adolescents that initiate and maintain cannabis use and those that do not. Distinct choice preferences may be supported by changes in the prefrontal cortex that modulate responses to prospective rewards and losses as well ambiguity. In adolescent cannabis abusers, alterations in prefrontal cortical (PFC) systems - such as the dorsolateral prefrontal cortex (dlPFC), orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC) - may contribute to preference for immediate small over larger delayed rewards through decreased modulation of striatal activity, preference for larger future losses over smaller immediate losses through reduced modulation of the amygdala (AMD) and Insula (INS), and selection of uncertain ambiguous over certain choices through decreased striatal modulation. This proposal aims to compare cannabis abusing adolescents and non-using healthy comparison subjects using functional magnetic resonance imaging (fMRI) to 1) evaluate neural systems potentially compromised in adolescent cannabis users during decision-making, 2) determine whether adolescent cannabis users, compared to healthy controls, show different patterns of choice during decision-making, and 3) evaluate whether age related decreases in reward discounting that normally occur in adolescence are disrupted in cannabis abusers. Findings from these studies may provide new insights for the development of drug use prevention strategies.) PUBLIC HEALTH RELEVANCE: This project will use functional magnetic resonance imaging to gain insight into neural systems underlying decision-making processes compromised in cannabis abusing adolescents. The results of the study will contribute to basic knowledge about the neural basis of choice preference in substance abusing adolescents, inform drug prevention strategies, and provide preliminary data for more extensive future proposals